Field of the Invention
This invention relates to a mesalamine pharmaceutical composition. In particular, it relates to a mesalamine pharmaceutical composition that has a reduced delivery variability.
Description of Related Art
The advantages of delivery of therapeutic agents to the lower part of the gastrointestinal tract, especially the large intestine or the colon, are well known. Several references illustrate the difficulty of formulating dosage forms that will achieve this delivery benefit. For example, U.S. Pat. Nos. 5,541,170 and 5,541,171 (both Rhodes et al.) discuss the delivery of pharmacologically active agents, especially 5-aminosalicylic acid, to the large intestine for the treatment of colonic or rectal disorders. U.S. Pat. No. 5,686,105 (Kelm et al.) teaches colonic delivery of therapeutic agents wherein the dosage form comprises a coating system with at least one inner coating layer and one outer coating layer. The inner coating layer is an enteric polymer that begins to dissolve in an aqueous media at a pH between about 5 to about 6.3, and the outer coating layer is an enteric polymer that begins to dissolve in an aqueous media at a pH of between about 6.8 to 7.2. U.S. Pat. No. 5,171,580 (Iamartino et al.) teaches pharmaceutical preparations containing an active ingredient to be released in the lower part of the gastrointestinal tract, the large intestine and especially the colon, consisting of a core with the active, the core being coated with three protective layers at different solubilities. This reference focuses on providing more specific and reliable release of a therapeutic active agent to the lower part of the gastrointestinal tract, especially the colon, achieved with the three protection layers, as well as the benefits of having a selective effect in the colon.
Other references also focus on the benefits of delivering therapeutic agents to the colon. These references include U.S. Pat. No. 5,686,106 (Kelm et al.), U.S. Pat. No. 5,914,132 (Kelm et al.), U.S. Pat. No. 4,910,021 (Davis et al.), U.S. Pat. No. 4,432,966 (Zeitoun et al.), U.S. Pat. No. 5,654,004 (Okayama et al.), U.S. Pat. No. 5,900,252 (Calcanchi et al.), U.S. Pat. No. 5,482,718 (Shah et al.), U.S. Pat. No. 5,316,772 (Jurgens et al.), U.S. Pat. No. 5,401,512 (Rhodes et al.), EP 225,189 (Davies, et al.), EP 1315481 (Lutolf et al.), and Khan et al., Drug Development and Industrial Pharmacy, 26(5), 549-554 (2000).
U.S. Pat. No. 6,893,662 (Dittmar et al.) teaches a solid unit dosage form for oral administration which minimizes the impact or negative effects of coating fractures, especially for larger or heavier unit dosage forms.
The problem of mesalamine tablets and other similar tablets passing through the gut intact have been described in Sinha et al., Pract. Gastroenterol., 27, 56-69 (2003), Safdi, Am. J. Gasteroenterol., 5159 (2005), Ibekwa et al., J. Pharm. Sci., 308, 52-60 (2006), and Ibekwa et al., Pharm. Res., 25, 1828-1835 (2008). McConnell et al., Intl. J. Pharms., 364, 213-226 (2008) have found that due to variations in the physiology of the gastrointestinal tract from person to person, the failure to disintegrate may be due to the target pH not being reached in some subjects or not being high enough for a long time for the pH-responsive film coating to dissolve. Such failure to disintegrate results in delivery variability of the mesalamine pharmaceutical compositions.
Accordingly, there remains a need for mesalamine pharmaceutical composition which reduces delivery variability by minimizing the failure to disintegrate.